High electrolyte content W/O emulsions for treating irritated/sensitive skins

ABSTRACT

Stable, topically applicable water-in-oil emulsions, well suited for therapeutically treating irritated/sensitive skins and having high electrolyte content, comprise (a) at least 2% by weight of at least one water-soluble metal salt, (b) at least one hydrophobic gelling agent, (c) less than 5% by weight of at least one emulsifying agent, and, advantageously, at least one biologically active agent, for example an active agent that modulates skin differentiation and/or proliferation and/or pigmentation, an anti-inflammatory, an antibacterial, an antifungal, etc., and/or at least one keratolytic active agent, neuropeptide antagonist and/or inflammation-mediator antagonist.

CROSS-REFERENCE TO RELATED APPLICATION

[0001] This application is a divisional of U.S. application Ser. No.08/943,191, filed Oct. 3, 1997, incorporated by reference herein in itsentirety and relied upon.

BACKGROUND OF THE INVENTION

[0002] 1. Technical Field of the Invention

[0003] The present invention relates to stable water-in-oil emulsionshaving a high electrolyte content, comprising at least 2% by weight,relative to the total weight of the composition, of a water-solublemetal salt, at least one hydrophobic gelling agent and an amount of asuitable emulsifying system effective to provide a stable composition,particularly a stable topically applicable composition.

[0004] This invention also relates to dermocosmetic compositionscomprising the above stable w/o emulsions, for treating pathologicaland/or physiological disorders associated with the release of substanceP and/or of TNF-alpha (Tumor Necrosis Factor-alpha) and, in particular,for treating sensitive skin and skin disorders and diseases in whichpruritus, acne rosacea and/or discreet erythema exist.

[0005] 2. Description of the Prior Art

[0006] It is known to this art that certain skin types are moresensitive than others. The symptoms of sensitive skin were hithertopoorly characterized and the problem of these skin types wasconsequently poorly defined since it was unknown exactly what processwas involved in skin sensitivity/nonallergic hyperreactivity of theskin. Certain researchers considered that sensitive skin was a skinwhich reacted to cosmetic and/or dermatological products, while othersconsidered that it was a skin which reacted to various external factors,not necessarily associated with cosmetic and/or dermatological products.

[0007] Certain tests have been conducted in an effort to characterizesensitive skin, for example tests using lactic acid and DMSO which areknown irritants: see, for example, the article by K. Lammintausta etal., Dermatoses, 36, pages 45-49 (1988); and the article by T. Agner andJ. Serup, Clinical and Experimental Dermatology, 14, pages 214-217(1989). However, these tests did not permit the characterization ofsensitive skin, which was likened to allergic skin.

[0008] The symptoms associated with sensitive skin were demonstrated anddescribed in FR-95/04,268 filed Apr. 10, 1995 and assigned to theassignee hereof. These symptoms are, in particular, subjective signs,which are essentially dysaesthetic sensations. By the term “dysaestheticsensations” are intended the more or less painful sensations experiencedin a region of skin, such as stinging, tingling, itching or pruritus,burning, heating, discomfort, tautness, etc.

[0009] It has also been shown that a sensitive skin was not an allergicskin, since an allergic skin is a skin which reacts to an externalagent, an allergen, which triggers an allergic reaction. This is animmunological process which occurs only when an allergen is present andwhich affects only sensitized individuals. In contrast, the essentialcharacteristic of sensitive skin is a mechanism of response to externalfactors, which may affect any individual, although individuals withso-called sensitive skin react faster thereto than others. Thismechanism is not immunological, but aspecific.

[0010] Sensitive skin may be divided into two major clinical categories,irritable skin and intolerant skin. An irritable skin is a skin whichreacts, via pruritus, namely, by itching or by stinging, to variousfactors such as the environment, emotions, foods, the wind, rubbing,shaving, hard water having a high calcium concentration, temperaturevariations or wool. In general, these signs are associated with a dryskin with or without dartres, or with a skin which displays an erythema.An intolerant skin is a skin which reacts, by sensations of heating,tautness, tingling and/or redness, to various factors such as theapplication of cosmetic or dermatological products or soap. In general,these signs are associated with an erythema and with a hyperseborrhoeicor acneic skin, or even a rosaceiform skin, with or without dartres.

[0011] In general, sensitive skin is defined by a specific reactivity ofthe skin. This hyperreactivity may, in particular, be induced byenvironmental, emotional and dietary factors or, alternatively, by theapplication of or contact with cosmetic or dermatological products. Thishyperreactive state which defines sensitive skin distinguishes such skinfrom the ubiquitous reactivity occasioned by irritant agents whichinduce a skin irritation in almost all individuals.

[0012] This hyperreactive state is experienced and recognized byindividuals suffering therefrom as a “sensitive skin.”

[0013] “Sensitive” scalps have a more univocal clinical semiology: thesensations of pruritus and/or of stinging and/or of heating areessentially triggered by local factors such as rubbing, soap,surfactants, hard water having a high calcium concentration, shampoos orlotions. These sensations are also in certain instances triggered byfactors such as the environment, emotions and/or foods. Erythema andhyperseborrhoea of the scalp and the presence of dandruff are oftenassociated with the above signs.

[0014] Moreover, in certain anatomical regions such as the major folds(groin, genital, axillary, popliteal, anal and submammary regions, andin the crook of the elbow) and the feet, sensitive skin is reflected inpruriginous sensations and/or dysaesthetic sensations (heating,stinging) associated, in particular, with sweat, rubbing, wool,surfactants, hard water having a high calcium concentration and/ortemperature variations.

[0015] Pruritus is a common symptom of dermatitis, which often causesconsiderable inconvenience to the patient. When the pruritus is verysevere, the inconvenience may be such that the patient cannot continuehis or her usual activity. In addition, pruritus may be a source ofcomplications: excoriations which may become overinfected,lichenification of the pruriginous regions, the consequence of which isto position the patient in a veritable vicious circle. Among the formsof dermatitis often associated with pruritus, exemplary are eczema,atopic dermatitis, contact dermatitis, flat lichens, prurigo, urticariapruriginous toxidermias and certain clinical forms of psoriasis.

[0016] Pruritus is sometimes the predominant pathological skin sign, asin the case of aquagenic pruritus, pruritus of the scalp while dandruffis present (pityriasis capitis), pruritus of blood dialysis patients,renal insufficiency, AIDS sufferers and individuals suffering frombiliary obstructions, or pruritus of the paraneoplastic manifestationsof certain cancers.

[0017] Further, pruritus is a sign often encountered over the course ofcertain parasitic attacks on the skin, or generally. These may be, forexample, scabies, filariasis, oxyuriasis or demodicidosis of the skin.

[0018] Since the characteristics of sensitive skin are poorlyunderstood, it was hitherto very difficult to treat it, and it wastreated indirectly, for example by limiting the use of products irritantin nature, such as surfactants, preservatives or fragrances, as well ascertain active agents, in cosmetic or dermatological compositions.

[0019] To date, pruritus was treated using emollient preparations, localcorticoids, PUVA therapy or antihistamines. Local corticoids are,admittedly, very effective for alleviating the symptoms, but theireffect is, unfortunately, not immediate. Too, they often elicit verysevere side effects such as atrophy, and expose the patient to risks ofmycosal and/or bacterial infections. PUVA therapy is the localirradiation of the diseased skin with UVA radiation, after absorption ofa photosensitizing species (psoralen). This technique presents the majordrawback of photoaging which may result in skin cancers. Further, thistreatment is not ambulatory, thus obliging patients to regularly visit aspecialized center throughout the treatment period, which is veryrestrictive and limits their professional activity. Emollients elicit avery modest anti-pruriginous effect and are of poor efficacy when thepruritus is considerable. Moreover, antihistamines are not of constantefficacy and must be administered orally.

[0020] Thus, serious need continues to exist in this art for improvedtreatment of the above skin afflictions which does present the abovedrawbacks.

[0021] The use of at least one metal salt, in particular an alkalineearth metal salt, for treating pruritus or “sensitive skin” problemseffectively while at the same time avoiding the drawbacks indicatedabove is described in FR-95/04,268, filed Apr. 10, 1995 and assigned tothe assignee hereof.

[0022] Gelled compositions having a high electrolyte content aredescribed in FR-96/00,742 and FR-96/03,094, filed Jan. 27, 1996 and Mar.12, 1996, respectively, also assigned to the assignee hereof.

[0023] In the cosmetic or dermatological field, it is common totopically apply creams consisting of a W/o emulsion containing anaqueous phase dispersed in an oily phase. These emulsions often havestability problems, which makes them difficult to formulate. Thus,various means have been attempted to overcome this drawback. One suchmeans entails greatly increasing the emulsifier content of theseemulsions. However, it is known that emulsifiers used in large amountscan elicit irritant effects on certain skin types. Moreover, as above,the creams obtained are often compact and heavy. It will readily beappreciated that such compositions are not suitable for application tosensitive skin, given the difficulties indicated above.

[0024] Various W/O emulsion compositions having a high electrolytecontent are known to this art. Thus, EP-530,531 (Benckiser) describes acosmetic composition formulated as an O/W or W/O emulsion comprising anemulsifying system and at least 2% (preferably at least 5%) of awater-soluble salt of alkali metals or of alkaline earth metals. Thesalt is preferably a magnesium salt, which serves as a preservative.These emulsions can be formulated into cosmetic compositions devoid ofpreservatives. For the W/O emulsions, the emulsifying system includes 5%to 10% by weight of the combination of a glycerol ester and of acopolymer of polyether alkyl silicones and a fatty acid ester.

[0025] Similarly, U.S. Pat. No. 5,162,378 (Revlon) describes a W/Omicroemulsion including 8% to 20% of an alkali metal or alkaline earthmetal salt, 20% to 40% of water and 8% to 20% of an emulsifying systemconsisting of cetyl dimethicone copolyol, optionally supplemented withhexyl laurate and polyglyceryl-4 isostearate. These compositionscomprising a high emulsifier content and a limited amount of water arenot suitable for application to sensitive skin either.

SUMMARY OF THE INVENTION

[0026] Accordingly, a major object of the present invention is theprovision of novel stable water-in-oil (W/O) emulsions having highelectrolyte content, well suited for topical application, andparticularly effective for treating “sensitive skin” afflictions,especially pruritis.

[0027] This invention also provides cosmetic/dermatological compositionsformulated from the subject novel W/O emulsions.

[0028] Briefly, the present invention features novel, stable W/Oemulsions having a high electrolyte content, comprising at least 2% byweight, preferably at least 3% by weight and more preferably at least 5%by weight, relative to the total weight of the composition, of at leastone water-soluble metal salt, at least one hydrophobic gelling agent andless than 5% by weight, also relative to the total weight of thecomposition, of a suitable emulsifying system.

DETAILED DESCRIPTION OF BEST MODE AND SPECIFIC/PREFERRED EMBODIMENTS OFTHE INVENTION

[0029] More particularly ccording to the present invention, by the term“metal salt” is intended a salt of a metal, namely, a simple compoundcapable of liberating simple metal cations (Dictionnaire de la Chimie etde ses Applications, Duval & Duval, 3rd edition, 1978, Technique etDocumentation).

[0030] The water-soluble metal salts are more particularly selected fromamong the water-soluble salts of alkali metals, or alkaline earthmetals, of transition metals and of metals from Groups 13 and 14 of thePeriodic Table.

[0031] Exemplary water-soluble salts of alkali metals according to theinvention include, in particular, the lithium, sodium and potassiumsalts.

[0032] Exemplary water-soluble salts of alkaline earth metals accordingto the invention include, in particular, the beryllium, magnesium,calcium, strontium and/or barium salts.

[0033] Exemplary water-soluble salts of transition metals according tothe invention include, in particular, the lanthanide salts and the saltsof metals of the fourth period of the Periodic Table of the Elements,such as the magnesium, cobalt and zinc salts.

[0034] And exemplary water-soluble salts of metals from groups 13 and 14of the Periodic Table of the Elements according to the invention includethe aluminum and tin salts.

[0035] By the term “lanthanide” is intended the elements of atomicnumber z ranging from 57 to 71, i.e., lanthanum, cerium, praseodymium,neodymium, promethium, samarium, europium, gadolinium, terbium,dysprosium, holmium, erbium, thulium, ytterbium and lutetium.

[0036] Preferably, the water-soluble metal salts of this invention areselected from among the lithium, strontium, barium, yttrium, neodymium,gadolinium, manganese and zinc salts, more preferably the strontiumsalts.

[0037] These salts may be, for example, carbonates, bicarbonates,sulfates, glycerophosphates, borates, chlorides, nitrates, acetates,hydroxides and persulfates, as well as salts of α-hydroxy acids or saltsof fruit acids (citrate, tartrate, lactate, malate), or salts of aminoacids (aspartate, arginate, glucocholate, fumarate), or salts of fattyacids (palmitate, oleate, caseinate, behenate).

[0038] Preferably, the salts are selected from among the nitrates andchlorides, in particular lithium, strontium, barium, yttrium, neodymium,gadolinium, manganese or zinc nitrate, lithium, strontium, barium,yttrium, neodymium, gadolinium, manganese and zinc chloride, andsulfates and acetates, such as calcium, strontium and magnesium sulfateand strontium and magnesium acetate.

[0039] Advantageously, the amount of water-soluble metal salts in theemulsions according to the invention ranges from 2% to 20% by weightrelative to the total weight of the composition, preferably from 5% to10% by weight.

[0040] By the expression “suitable emulsifying system” is intended anyemulsifying agent or mixture of emulsifying agents capable of providinga stable W/O emulsion having a high electrolyte content when they arepresent in the composition in an amount of less than 5% by weightrelative to the total weight of the composition.

[0041] According to this invention, the expression “stable W/O emulsion”preferably connotes an emulsion which remains stable for at least 1month at 45° C.

[0042] Advantageously, the suitable emulsifying system comprises atleast one glycerol ester and/or at least one silicone polymer, which aresuitable for the preparation of W/O emulsions.

[0043] Preferably, the glycerol ester is a polyglycerol ester of a fattyacid, in particular a polyglycerol ester of (iso)stearic acid, such aspolyglyceryl-n isostearates, wherein n is an integer ranging from 2 to6, marketed under the trademark Isolan by Goldschmidt.

[0044] Advantageously, the silicone polymer suitable for the preparationof an W/O emulsion is a polysiloxane, preferably a copolymer ofpolysiloxane polyalkyl polyethers, such as those described inDE-3,622,571, EP-125,779, EP-310,903 and EP-537,003 or in U.S. Pat. Nos.4,421,656, 4,218,250, 4,268,499, 4,311,695, 4,122,029, 4,268,499 and5,008,103. These are, more particularly, copolymers such as cetyldimethicone copolyol, marketed under the trademark Abil by Goldschmidtor lauryl methicone copolyol marketed under the trademark DC5200 by DowCorning.

[0045] Preferably, the suitable emulsifying system comprises at leastone silicone polymer, which is suitable for the preparation of W/Oemulsions, either singly or in combination with at least one glycerolester.

[0046] When used in combination, the glycerol ester/silicone weightratio advantageously ranges from 1/1 to 1/10, more preferably about 1/5.

[0047] Preferably, the amount of suitable emulsifying system ranges from2% to 4% by weight relative to the total weight of the composition.

[0048] In addition, the emulsions according to the invention comprise atleast one hydrophobic gelling agent. Exemplary such hydrophobic gellingagents include the modified clays such as bentones, silica, inparticular hydrophobic silica, such as silyl or dimethylsilyl silica(“silica silylate” or “silica dimethyl silylate”) marketed under thetrademarks Aerosil R 812, R 972 or R 974 by Degussa, glycol esterderivatives of fatty acids, such as acetylated glycol stearate,optionally associated with a glycerol mono-, di- or triester of a fattyacid, such as tristearine, in particular the acetylated glycolstearate/tristearine mixture marketed under the trademark Unitwix byGuardian. The gelling agent is preferably silyl or dimethylsilyl silicaor Unitwix.

[0049] The amount of hydrophobic gelling agent advantageously rangesfrom 0.01% to 5% by weight relative to the total weight of thecomposition, preferably from 0.1% to 3% by weight.

[0050] The aqueous phase of the emulsions according to the invention maycomprise water, purified water, a floral water such as cornflower water,or a natural mineral or spring water, and mixtures thereof. For example,the natural mineral or spring water may be selected from among eau deVittel, the waters of the Vichy basin, eau d'Uriage, eau de la RochePosay, eau de la Bourboule, eau d'Enghien-les-Bains, eau de SaintGervais-les-Bains, eau de Néris-les-Bains, eau d'Allevard-les-Bains, eaude Digne, eau de Maizières, eau de Neyrac-les-Bains, eau deLons-le-Saunier, les Eaux Bonnes, eau de Rochefort, eau de SaintChristau, eau des Fumades, eau de Tercis-les-Bains, eau d'Avène and eaud'Aix-les-Bains.

[0051] The aqueous phase preferably comprises a spring water which isknown for its soothing, anti-irritant, anti-free-radical properties whenapplied to the skin, in particular eau de la Roche Posay. Such springwaters generally have a high electrolyte content, in particularcomprising water-soluble salts of alkaline earth metals. Obviously, theamount of alkaline earth metals in the spring water will be taken intoaccount in order to determine the total amount of alkaline earth metalsin the emulsions according to the invention.

[0052] The aqueous phase is advantageously present in an amount rangingfrom 40% to 80% by weight relative to the total weight of thecomposition, preferably from 50% to 70% by weight.

[0053] The fatty phase of the emulsions according to the invention maycomprise fatty substances conventionally employed in the intended fieldof application. Exemplary of these are the silicone fatty substancessuch as silicone oils, as well as non-silicone fatty substances such asplant oils, mineral oils, animal oils or synthetic oils.

[0054] Representative silicone fatty substances are:

[0055] (i) poly(C₁-C₂₀)alkylsiloxanes and, in particular, thosecontaining terminal trimethylsilyl groups, including the linearpolydimethylsiloxanes (PDMS) and alkylmethylpolysiloxanes such as cetyldimethicone (CTFA name),

[0056] (ii) volatile silicone oils such as:

[0057] (a) cyclic volatile silicones having from 3 to 8 and preferablyfrom 4 to 6 silicon atoms; these include, for example,cyclotetradimethylsiloxane, cyclopentadimethylsiloxane andcyclohexadimethylsiloxane,

[0058] (b) linear volatile silicones having from 2 to 9 silicon atoms;these include, for example, hexamethyldisiloxane, hexylheptamethyltrisiloxane and octyl heptamethyltrisiloxane.

[0059] Exemplary non-silicone fatty substances include the usual oils,such as liquid paraffin, liquid petroleum jelly, almond oil,perhydrosqualene, apricot oil, wheatgerm oil, sweet almond oil,beauty-leaf oil, palm oil, castor oil, avocado oil, jojoba oil, oliveoil or cereal germ oil; esters of fatty acids or of fatty alcohols, suchas octyl dodecyl myristate or C₁₂-C₁₅ alkyl benzoates, alcohols;acetylglycerides; octanoates, decanoates or ricinoleates of alcohols orof polyalcohols; fatty acid triglycerides; glycerides; hydrogenatedpolyisobutene, hydrogenated oils that are solid at 25° C.; lanolins;fatty esters that are solid at 25° C.

[0060] These fatty substances are variously selected by one skilled inthis art in order to formulate a composition having the desiredproperties, for example in terms of consistency or texture.

[0061] Thus, the fatty phase of the emulsions according to the inventionis advantageously present in an amount ranging from 10% to 40% by weightrelative to the total weight of the composition and preferably from 20%to 35% by weight.

[0062] In addition, the emulsions according to the invention maycomprise at least one stabilizer which is suitable for a W/O emulsionhaving a high electrolyte content. Such stabilizers are selected, inparticular, from among the alkali metal salts, for example sodiumchloride, waxes and mixtures thereof in all proportions.

[0063] Exemplary waxes which are suitable stabilizers according to theinvention include animal waxes, plant waxes, mineral waxes and syntheticwaxes such as microcrystalline waxes, paraffin, petrolatum, petroleumjelly, ozokerite, montan wax; beeswax, lanolin and derivatives thereof;candelilla wax, ouricurry wax, carnauba wax, Japan wax, cocoa butter,cork fiber wax or sugar cane wax; hydrogenated oils that are solid at25° C., ozokerites, fatty esters and glycerides that are solid at 25°C.; polyethylene waxes and the waxes obtained by Fischer-Tropschsynthesis; silicone waxes. Microcrystalline wax is the preferred.

[0064] The amount of stabilizer advantageously ranges from 0% to 5% byweight relative to the total weight of the composition, preferably from0% to 3% by weight.

[0065] The emulsions according to the invention are advantageouslyformulated as a cream, a milk, a lotion, etc.

[0066] In known manner, the emulsions of the invention may also containadditives and adjuvants that are common in the cosmetic and/ordermatological fields, such as preservatives, antioxidants, complexingagents, solvents, fragrances, fillers (for example a matt-effect agent),UV-screening agents, bactericides, odor absorbers, dyestuffs, colorants,etc. The amounts of these various additives and adjuvants are those thatare conventional in the field under consideration and, for example,comprise from 0.01 to 5% by weight relative to the total weight of thecomposition. Depending on their nature, these additives and adjuvantsmay be incorporated into the fatty phase or into the aqueous phase.

[0067] The emulsions/compositions according to the invention may alsocomprise at least one active agent which normally promotes a skinirritation.

[0068] The emulsions/compositions according to the invention are alsouseful for reducing the irritant effect of at least one active irritantcompound administered separately in a cosmetic or pharmaceuticalcomposition, topically (cream, lotion, gel, etc.) or systemically(orally, rectally or parenterally). The compositions according to theinvention may be topically applied to the skin at the same time that theirritant active agent is administered, or combined but spread out overtime.

[0069] Proteins or protein hydrolysates, amino acids, polyols, urea,allantoin, sugars and sugar derivatives, water-soluble vitamins, starchand bacterial or plant extracts, in particular those of Aloe vera, areexemplary hydrophilic active agents.

[0070] Retinol (vitamin A) and derivatives thereof, tocopherol (vitaminE) and derivatives thereof, essential fatty acids, ceramides andessential oils are exemplary lipophilic active agents.

[0071] These active agents are particularly intended for preventingand/or treating skin conditions/afflictions. Exemplary of these activeagents are:

[0072] (a) agents which modify the differentiation and/or proliferationand/or pigmentation of the skin, such as retinoic acid and isomersthereof, retinol and esters thereof, retinoids, in particular thosedescribed in FR-2,570,377, EP-199,636, EP-325,540 and EP-402,072,retinal, vitamin D and derivatives thereof, estrogens such as estradiol,kojic acid or hydroquinone;

[0073] (b) antibacterial agents such as clindamycin phosphate,erythromycin or antibiotics of the tetracycline class;

[0074] (c) antiparasitic agents, in particular metronidazole, crotamitonor pyrethroids;

[0075] (d) antifungal agents, in particular compounds belonging to theimidazole class, such as econazole, ketoconazole or miconazole or saltsthereof, polyene compounds such as amphotericin B, compounds of theallylamine family, such as terbinafine, or alternatively octopirox;

[0076] (e) steroidal anti-inflammatory agents such as hydrocortisone,betamethasone valerate or clobetasol propionate, or non-steroidalanti-inflammatory agents such as ibuprofen and salts thereof, diclofenacand salts thereof, acetylsalicylic acid, acetaminophen or glycyrrhetinicacid;

[0077] (f) anaesthetics such as lidocaine hydrochloride and derivativesthereof;

[0078] (g) antipruriginous agents such as thenaldine, trimeprazine orcyproheptadine;

[0079] (h) antiviral agents such as acyclovir;

[0080] (i) keratolytic agents such as alpha- and beta-hydroxycarboxylicor beta-ketocarboxylic acids, salts, amides or esters thereof and, moreparticularly, alpha-hydroxy acids such as glycolic acid, lactic acid,tartaric acid, malic acid, citric acid, mandelic acid and, in general,fruit acids, and beta-hydroxy acids such as salicylic acid andderivatives thereof, in particular alkyl derivatives, such as5-n-octanoylsalicylic acid;

[0081] (j) anti-free radical agents such as alpha-tocopherol or estersthereof, superoxide dismutases, certain metal chelating agents orascorbic acid and esters thereof;

[0082] (k) antiseborrhoeic agents such as progesterone;

[0083] (l) antidandruff agents such as octopirox or zinc pyrithione;

[0084] (m) antiacne agents such as retinoic acid or benzoyl peroxide;

[0085] (n) antimetabolites;

[0086] (o) agents for combating hair loss such as minoxidil;

[0087] (p) antiseptic agents.

[0088] The emulsions/compositions according to the invention may alsocomprise, as active agents therefor, at least one keratolytic agentand/or at least one neuropeptide antagonist and/or at least oneinflammation-mediator antagonist, various water-soluble metal salts, inparticular for treating sensitive skin.

[0089] The present invention thus also features stable W/O emulsionshaving a high electrolyte content, comprising at least 2% by weight,relative to the total weight of the composition, of at least onewater-soluble metal salt as described above, at least one activecompound selected from among keratolytic agents, neuropeptideantagonists and inflammation-mediator antagonists other thanwater-soluble metal salts, at least one hydrophobic gelling agent asdescribed above and a suitable emulsifying system, also as describedabove.

[0090] Exemplary keratolytic agents according to the invention includealpha- and beta-hydroxycarboxylic or beta-ketocarboxylic acids, salts,amides or esters thereof and more particularly alpha-hydroxy acids suchas glycolic acid, lactic acid, tartaric acid, malic acid, citric acid,mandelic acid and, in general, fruit acids, and beta-hydroxy acids suchas salicylic acid and derivatives thereof, in particular alkylderivatives, such as 5-n-octanoylsalicylic acid. Advantageously, thesekeratolytic agents are present in the emulsions/compositions accordingto the invention in amounts of up to 10% by weight relative to the totalweight of the composition, preferably from 0.1% to 5% by weight.

[0091] Exemplary neuropeptide antagonists include substance Pantagonists and CGRP antagonists, and exemplary inflammation-mediatorantagonists include antagonists of histamine, of interleukin 1 or ofTNFα. These antagonists are advantageously present in a proportion offrom 0.000001% to 10% by weight relative to the total weight of thecomposition and preferably from 0.0001% to 5%.

[0092] Advantageously, substance P, CGRP and/or interleukin 1 receptorantagonists are formulated into the subject emulsions/compositions.

[0093] Exemplary substance P antagonists according to the inventioninclude species of organic or inorganic origin which inhibit thereceptor binding of substance P or inhibit the synthesis and/or releaseof substance P by sensitive nerve fibers.

[0094] The substance P receptor antagonist may, in particular, be apeptide or a non-peptide derivative containing a hetero atom, and moreprecisely a compound containing a heterocycle or a hetero atom bondeddirectly or indirectly to a benzene ring.

[0095] For example, sendide and spantide II are exemplary substance Preceptor antagonist peptides.

[0096] The peptides described in U.S. Pat. Nos. 4,472,305, 4,839,465,EP-A-101,929, EP-A-333,174, EP-A-336,230, EP-A-394,989, EP-A-44,332,EP-A-498,069, EP-A-515,681, EP-A-517,589, WO-A-92/22,569 andGB-A-2,216,529 are also representative peptides.

[0097] The non-peptide substance P receptor antagonists which are usefulaccording to the invention include, in particular, heterocyclic,especially sulfur-containing, nitrogen-containing or oxygen-containingcompounds or compounds comprising a nitrogen atom bonded directly orindirectly to a benzene ring.

[0098] Exemplary such heterocyclic compounds are those described inEP-A-360,390, EP-A-429,366, EP-A-430,771, EP-A-499,313, EP-A-514,273,EP-A-514,274, EP-A-514,275, EP-A-514,276, EP-A-520,555, EP-A-528,495,EP-A-532,456, EP-A-545,478, EP-A-558,156, WO-A-90/05,525,WO-A-90/05,729, WO-A-91/18,878, WO-A-91/18,899, WO-A-92/12,151,WO-A-92/15,585, WO-A-92/17,449, WO-A-92/20,676, WO-A-93/00,330,WO-A-93/00,331, WO-A-93/01,159, WO-A-93/01,169, WO-A-93/01,170,WO-A-93/06,099, WO-A-93/09,116 and WO-A-94/08,997. In particular,compounds comprising at least one nitrogen-containing heterocycleinclude a 2-tricyclyl-2-aminoethane derivative, a spirolactamderivative, a quinuclidine derivative, an azacyclic derivative, anaminopyrrolidine derivative, a piperidine derivative, anaminoazaheterocycle and an isoindole derivative.

[0099] Exemplary compounds containing a nitrogen atom bonded directly orindirectly to a benzene ring include those described in EP-A-522,808 andWO-A-93/01,165.

[0100] And exemplary CGRP antagonists according to the invention includeany species or substrate of organic or inorganic origin that inhibitsthe receptor binding of CGRP or inhibits the synthesis and/or release ofCGRP by sensitive nerve fibers.

[0101] For an active species to be recognized as a CGRP antagonist, itmust, in particular, satisfy the following characteristic of exhibitingCGRP-antagonist pharmacological activity, namely, inducing a coherentpharmacological response, in particular, in one of the following tests:

[0102] (1) the antagonist substance should decrease the vasodilationinduced by capsaicin and/or

[0103] (2) the antagonist substance should inhibit the release of CGRPby sensitive nerve fibers and/or

[0104] (3) the antagonist substance should reduce inhibition of thecontraction of the smooth muscle of the deferent canal induced by CGRP.

[0105] In addition, the CGRP antagonist may have an affinity for CGRPreceptors.

[0106] CGRP 8-37, an anti-CGRP antibody, is an exemplary CGRP receptorantagonist according to the invention.

[0107] When the emulsions/compositions according to the inventioncomprise an active irritant compound that elicits skin irritation,selected from among keratolytic agents, neuropeptide antagonists andinflammation-mediator antagonists, other than water-soluble metal salts,the amount of emulsifying system will be effective to produce a stablecomposition, consistent with the stability criteria described above.Again, the minimum amount of emulsifying system is advantageouslyemployed that produces a stable composition. A “suitable amount ofemulsifying system” is thus an amount which is necessary and sufficientto provide a stable composition for at least 1 month at 45° C. Thisamount is preferably less than 10% by weight relative to the totalweight of the composition, more preferably less than 8% by weight.

[0108] In order to further illustrate the present invention and theadvantages thereof, the following specific examples are given, it beingunderstood that same are intended only as illustrative and in nowiselimitative.

[0109] In said examples to follow, all parts and percentages are givenby weight, unless otherwise indicated. EXAMPLE 1 The following W/O creamwas formulated: Ingredients % A: Fatty phase: Polyglyceryl-4 isostearate0.50 Cetyl dimethicone copolyol 2.50 C₁₂-C₁₅ alkyl benzoate 1.00Octyldodecanol 9.00 Aluminum starch octenyl succinate 3.00 Dicaprylylether 3.00 Aerosil R 812 1.00 B: Aqueous phase: Sodium chloride 0.50Spring water 69.20 Strontium chloride 6.00 Preservative 0.30 C:Auxiliary phase: Cyclomethicone 5.00

[0110] This W/O cream was formulated according to the followingprocedure:

[0111] (1) phases A and B were heated to 75° C. separately and phase Bwas then poured gradually into phase A at 600 rev/min;

[0112] (2) the mixture was permitted to cool with stirring at 600rev/min, to 40° C.;

[0113] (3) phase C was then added at 1,500 rev/min, after which theemulsion was stirred at 3,000 rev/min for 5 min.

[0114] An emulsion which was stable for at least 1 month at 45° C. wasobtained. EXAMPLE 2 The following W/O cream was formulated: Ingredients% A: Fatty phase: Polyglyceryl-4 isostearate 0.50 Cetyl dimethiconecopolyol 2.50 C₁₂-C₁₅ alkyl benzoate 3.00 Capryloylsalicylic acid 1.00Octyldodecanol 11.00 Aluminum starch octenyl succinate 3.00 Dicaprylylether 3.00 Acetylated and tristearine glyceryl 1.50 stearate (UNITWIX)B: Aqueous phase: Spring water 62.00 Strontium chloride 6.60Preservative 0.90 C: Auxiliary phase: Cyclomethicone 5.00

[0115] The emulsion was formulated according to the procedure ofExample 1. A composition which was stable for at least 1 month at 45° C.was also obtained. EXAMPLE 3 The following W/O cream was formulated:Ingredients % A: Fatty phase: Polyglyceryl-4 isostearate 0.50 Cetyldimethicone copolyol 2.50 C₁₂-C₁₅ alkyl benzoate 3.00 Capryloylsalicylicacid 1.00 2-Hexyldecanol, 2-octyldecanol, 11.00 2-hexyldodecanol and2-octyldodecanol Aluminum starch octenyl succinate 3.00 Dicaprylyl ether3.00 Stabilizer 3.00 B: Aqueous phase: Spring water 60.50 Strontiumchloride 6.60 Preserving agent 0.90 C: Auxiliary phase: Cyclomethicone5.00

[0116] The emulsion was formulated according to the procedure ofExample 1. A composition which was stable for at least 1 month at 45° C.was also obtained.

[0117] The W/O emulsions according to the invention exhibited bettertolerance for alkaline earth metal salts than the corresponding O/Wemulsions, for individuals suffering from pruritus.

[0118] While the invention has been described in terms of variouspreferred embodiments, the skilled artisan will appreciate that variousmodifications, substitutions, omissions, and changes may be made withoutdeparting from the spirit thereof. Accordingly, it is intended that thescope of the present invention be limited solely by the scope of thefollowing claims, including equivalents thereof.

What is claimed is:
 1. A regimen for treating the sensitive/irritatedskin of an individual in need of such treatment, comprising topicallyapplying thereto an effective amount of a stable water-in-oil emulsionsuited for topical application to irritated/sensitive skins and having ahigh electrolyte content, comprising: (a) at least one water-solublemetal salt, in an amount of at least 2% by weight; (b) at least onehydrophobic gelling agent; and (c) at least one emulsifying agent, in anamount of less than 5% by weight.
 2. A regimen for treating thesensitive/irritated skin of an individual in need of such treatment,comprising topically applying thereto an effective amount of adermocosmetic composition comprising a stable water-in-oil emulsionsuited for topical application to irritated/sensitive skins and having ahigh electrolyte content, comprising: (a) at least one water-solublemetal salt, in an amount of at least 2% by weight; (b) at least onehydrophobic gelling agent; and (c) at least one emulsifying agent, in anamount of less than 5% by weight.
 3. A regimen according to claim 1,wherein said water-in-oil emulsion comprises at least one biologicallyactive agent selected from the group consisting of an agent formodulating skin differentiation and/or proliferation and/orpigmentation, an antibacterial agent, an antiparasitic agent, anantifungal agent, a steroidal anti-inflammatory agent, a non-steroidalanti-inflammatory agent, an anaesthetic agent, an antipruritic agent, anantiviral agent, a keratolytic agent, an anti-free radical agent, anantiseborrhoeic agent, an antidandruff agent, an anti-acne agent, anantimetabolite, an agent for combating hair loss, an antiseptic orcombination thereof.
 4. A regimen according to claim 1, wherein saidwater-in-oil emulsion further comprises at least one keratolytic activeagent, and/or at least one neuropeptide antagonist, and/or at least oneinflammation-mediator antagonist, other than a water-soluble metal salt.5. A regimen according to claim 4, wherein said water-in-oil emulsioncomprises at least one alpha- or beta-hydroxycarboxylic orbeta-ketocarboxylic acid, or salt, amide or ester thereof.
 6. A regimenaccording to claim 4, wherein said water-in-oil emulsion furthercomprises at least one substance P antagonist and/or at least one CGRPantagonist.
 7. A regimen according to claim 4, wherein said water-in-oilemulsion further comprises at least one antagonist of histamine,interleukin 1, and/or TNFα.
 8. The regimen according to claim 1, whereinsaid water-in-oil emulsion comprises at least 3% by weight of said atleast one water-soluble metal salt (a).
 9. The regimen according toclaim 8, wherein said water-in-oil emulsion comprises at least 5% byweight of said at least one water-soluble metal salt (a).
 10. Theregimen according to claim 1, wherein said at least one water-solublemetal salt (a) comprises a water-soluble salt of an alkali metal, of analkaline earth metal, of a transition metal and/or of a metal fromGroups 13 and 14 of the Periodic Table.
 11. The regimen according toclaim 10, wherein said at least one water-soluble metal salt (a)comprises a lithium, strontium, barium, yttrium, neodymium, gadolinium,manganese and/or zinc salt.
 12. The regimen according to claim 1,wherein said at least one water-soluble metal salt (a) comprises acarbonate, bicarbonate, sulfate, glycerophosphate, borate, chloride,nitrate, acetate, hydroxide, persulfate, salt of an α-hydroxy acid, saltof an amino acid and/or a salt of a fatty acid.
 13. The regimenaccording to claim 1, wherein said water-in-oil emulsion comprises from2% to 20% by weight of said at least one water-soluble metal salt (a).14. The regimen according to claim 1, wherein said at least oneemulsifying agent (c) comprises at least one glycerol ester and/or atleast one silicone polymer.
 15. The regimen according to claim 14,wherein said at least one emulsifying agent (c) comprises at least onepolyglycerol ester of a fatty acid.
 16. The regimen according to claim14, wherein said at least one emulsifying agent (c) comprises at leastone polysiloxane.
 17. The regimen according to claim 16, wherein saidpolysiloxane comprises a copolymer of cetyl dimethicone and laurylmethicone copolyol.
 18. The regimen according to claim 14, wherein saidat least one emulsifying agent (c) comprises at least one siliconepolymer and at least one glycerol ester, the glycerol ester/siliconeweight ratio ranging from 1/1 to 1/10.
 19. The regimen according toclaim 1, wherein said water-in-oil emulsion comprises from 2% to 4% byweight of said at least one emulsifying agent (c).
 20. The regimenaccording to claim 1, wherein said at least one hydrophobic gellingagent (b) comprises a modified clay, hydrophobic silica and/or glycolester of a fatty acid.
 21. The regimen according to claim 20, whereinsaid at least one hydrophobic gelling agent (b) comprises admixture ofacetylated glycol sterate and a glycerol triester of a fatty acid. 22.The regimen according to claim 20, wherein said at least one hydrophobicgelling agent (b) comprises a silyl or dimethylsilyl silica.
 23. Theregimen according to claim 1, wherein said water-in-oil emulsioncomprises from 0.01% to 5% by weight of said at least one hydrophobicgelling agent (b).
 24. The regimen according to claim 1, wherein theaqueous phase of said water-in-oil emulsion comprises a purified water,a floral water, a natural mineral or spring water, or mixture thereof.25. The regimen according to claim 1, wherein the aqueous phase of saidwater-in-oil emulsion comprises from 40% to 80% by weight thereof. 26.The regimen according to claim 1, wherein the fatty phase of saidwater-in-oil emulsion comprises from 10% to 40% by weight thereof. 27.The regimen according to claim 11, wherein said at least onewater-soluble metal salt (a) comprises a strontium salt.
 28. The regimenaccording to claim 13, wherein said water-in-oil emulsion comprises from5% to 10% by weight of said at least one water-soluble metal salt (a).29. The regimen according to claim 15, wherein said polyglycerol esterof a fatty acid comprises a polyglycerol ester of (iso)stearic acid. 30.The regimen according to claim 16, wherein said polysiloxane comprisespolysiloxane polyalkyl polyether copolymer.
 31. The regimen according toclaim 1, wherein said water-in-oil emulsion further comprises at leastone active agent which normally promotes skin irritation.
 32. Theregimen according to claim 1, wherein said water-in-oil emulsioncomprises at least one biologically active agent.
 33. The regimenaccording to claim 1, wherein said water-in-oil emulsion furthercomprises at least one salt or wax stabilizer therefor.
 34. The regimenaccording to claim 1, wherein said water-in-oil emulsion comprises acream, milk, gel or lotion.
 35. A regimen for treating thesensitive/irritated skin of an individual in need of such treatment,comprising topically applying thereto an effective amount of a stablewater-in-oil emulsion suited for topical application toirritated/sensitive skins and having a high electrolyte content,comprising: (a) at least one water-soluble metal salt, in an amount ofat least 2% by weight; (b) at least one hydrophobic gelling agent whichis selected from the group consisting of a modified clay, a hydrophobicsilica and a glycol ester derivative of a fatty acid; and (c) at leastone glycerol ester emulsifying agent and at least one silicone polymeremulsifying agent, in a combined amount of less than 5% by weight.
 36. Aregimen for treating the sensitive/irritated skin of an individual inneed of such treatment, comprising topically applying thereto aneffective amount of a stable water-in-oil emulsion suited for topicalapplication to irritated/sensitive skins and having a high electrolytecontent, comprising: (a) at least one water-soluble metal salt, in anamount of at least 2% by weight; (b) at least one hydrophobic gellingagent comprising at least one member selected from the group consistingof a modified clay, a hydrophobic silica and a glycol ester of a fattyacid, in an amount of from 0.01% to 5% by weight; and (c) at least oneglycerol ester emulsifying agent and at least one silicone polymeremulsifying agent, in a combined amount effective to provide a stableemulsion, said amount being less than 5% by weight.
 37. A regimenaccording to claim 36, wherein said water-in-oil emulsion comprises atleast one biologically active agent selected from the group consistingof an agent for modulating skin differentiation and/or proliferationand/or pigmentation, an antibacterial agent, an antiparasitic agent, anantifungal agent, a steroidal anti-inflammatory agent, a non-steroidalanti-inflammatory agent, an anaesthetic agent, an antipruritic agent, anantiviral agent, a keratolytic agent, an anti-free radical agent, anantiseborrboeic agent, an antidandruff agent, an anti-acne agent, anantimetabolite, an agent for combating hair loss, an antiseptic orcombination thereof.
 38. A regimen according to claim 36, wherein saidwater-in-oil emulsion further comprises at least one keratolytic activeagent, and/or at least one neuropeptide antagonist, and/or at least oneinflammation-mediator antagonist, other than a water-soluble salt.
 39. Aregimen according to claim 38, wherein said water-in-oil emulsioncomprises at least one alpha- or beta-hydroxycarboxylic orbeta-ketocarboxylic acid, or salt, amide or ester thereof.
 40. A regimenaccording to claim 38, wherein said water-in-oil emulsion furthercomprises at least one substance P antagonist and/or at least one CGRPantagonist.
 41. A regimen according to claim 38, wherein saidwater-in-oil emulsion further comprises at least one antagonist ofhistamine, interleukin 1 and/or TNFα.